Osel was founded to develop and commercialize a novel approach to prevent vaginal HIV transmission in women. We propose to interfere with HIV transmission by colonizing the vaginal mucosa with nonpathogenic lactobacilli genetically modified to bind and inactivate HIV. CD4- expressing lactobacilli should bind HIV in an irreversible manner, and inactive the virus by either bacterial hydrogen peroxide production, physical disruption of the viral particle, or removal of bound HIV from the body by normal sloughing of mucosal bacteria. Thus, the presence of the modified bacteria should reduce or eliminate HIV particles introduced by semen, thereby significantly reducing or eliminating the risk of viral transmission. This novel approach would create a barrier to viral transmission that is different from traditional vaccines. Therefore, it should act synergistically with vaccines, condoms, or other potential methods of protection. In addition, it would be female-controlled and particularly suited for use in economically disadvantaged populations and regions due to its ease of production and distribution. The underlying concept is generally applicable to other viruses that infect at other anatomical sites, such as respiratory or intestinal mucosa. The work being proposed include the genetic modifications of lactobacilli and to test their abilities to neutralize HIV in vitro. PROPOSED COMMERCIAL APPLICATIONS: Osel intends the ViroShield product (CD4-expressing non-pathogenic lactobacilli) to be marketed to sexually-active females worldwide to prevent the vaginal transmission of HIV. It will be marketed as a vaginal suppository, which is easy to use and female controlled. We expect that this product will be consumer-driven in developed countries and distributed by government health organizations in developing counties.